T-cell receptor rearrangement excision circles (TRECs) as a marker of thymic function

摘要

The thymus is crucial in the reconstitution of the T-cell compartment following lymphodepletion and also in establishing a normal, diverse T-cell receptor (TCR) repertoire after immune response to antigens. TCRαβ diversity is generated through rearrangements of the TCR alpha and TCR beta chain genes. The TCR delta chain locus lies within the TCR alpha chain locus and its excision forms the first step in TCR alpha chain gene rearrangement. The intervening excised DNA is circularized by the formation of a “signal joint” forming a DNA episome, termed a signal-joint T-cell receptor excision circle (sjTREC). Approximately 70% of T cells emerging from the thymus contain one or two sjTRECs – depending on whether one or both TCRα loci genes are rearranged. As these long-lived na?ve T cells mature and proliferate, their sjTRECs are stable and do not divide. The thymus contributes na?ve T (CD45RA+) cells with TRECs to the peripheral immune system, but memory T cells (CD45RO+) contain few if any detectable TRECs. Quantification of thymic function is clinically relevant in settings with immunodeficiencies, after HSCT, during HIV therapy as well as in autoimmune patients. In humans there is no specific phenotypic marker for recent thymic emigrants, therefore the use of real-time quantitative PCR methods for absolute TREC quantification provides a good tool for estimating recent thymic function in different clinical situations.